POS1166 IDENTIFICATION OF KEY GENES AND IMBALANCE OF IMMUNE CELL INFILTRATION IN IMMUNOGLOBULIN A ASSOCIATED VASCULITIS NEPHRITIS BY INTEGRATED BIOINFORMATIC ANALYSIS
Authors: X. MA, X. Jia, H. Zhu, R. Wang, Y. Shan
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Immunoglobulin A associated vasculitis (IgAV), also known as Henoch-Schonlein purpura, is a common systemic vascular inflammatory disease that chiefly manifests as skin purpura, arthritis, abdominal pain, gastrointestinal bleeding, and kidney involvement [1]. It is characterized by immunoglobulin A-dominant immune deposition in small blood vessels, and the excessive production of various inflammatory molecules [2]. Although the etiology and pathogenesis of IgAV are not fully understood, there is increasing evidence that infection, genetic susceptibility, and immune response disorders are closely related to the development and progression of IgAV [3,4]. Meawhile, abnormal expression of immune factors and imbalance of immune cell differentiation in general circulation may play crucial roles in the pathogenesis of IgAV [5]. Therefore, it is necessary to identify key pathways and immune cells in vasculitis, and to assess the significance of the immune microenvironment in the pathogenesis of IgAV. <h3>Objectives</h3> This study attempted to identify differentially expressed genes (DEGs) and find dysregulated immune cell types in IgAV to find the underlying pathogenesis for IgAV to the effective prediction of therapeutic targets in the future. <h3>Methods</h3> GSE102114 datasets were obtained from the Gene Expression Omnibus (GEO) database to identify DEGs. Then, the protein-protein interaction (PPI) network of the DEGs was constructed using the STRING database. And key hub genes were identified by cytoHubba plug-in, performed functional enrichment analyses and followed by verification using PCR based on patient samples. Finally, the abundance of 24 immune cells were detected by Immune Cell Abundance Identifier (ImmuCellAI) to estimate the proportions and dysregulation of immune cell types within IgAV. <h3>Results</h3> A total of 4200 DEGs were screened in IgAV patients compared to Health Donor, including 2004 upregulated and 2196 downregulated genes. Of the top 10 hub genes from PPI network, <i>STAT1</i>, <i>TLR4</i>, <i>PTEN</i>, <i>UBB</i>, <i>HSPA8</i>, <i>ATP5B</i>, <i>UBA52</i>, and <i>CDC42</i> were verified significantly upregulated in more patients. Enrichment analyses indicated that hub genes were primarily enriched in Toll-like receptor (TLR) signaling pathway, nucleotide oligomerization domain (NOD)-like receptor signaling pathway, and Th17 signaling pathways. Moreover, we found a diversity of immune cells in IgAV, consisting mainly of T cells. Finally, this study suggests that the overdifferentiation of Th2 cells, Th17 cells and Tfh cells may be involved in the occurrence and development of IgAV. <h3>Conclusion</h3> We screened out the key genes, pathways and maladjusted immune cells and associated with the pathogenesis of IgAV. The unique characteristics of IgAV-infiltrating immune cell subsets were confirmed, providing new insights for future molecular targeted therapy and a direction for immunological research on IgAV. <h3>References</h3> [1]Gedalia A. Henoch-Schonlein purpura. Curr Rheumatol Rep. 2004, 6(3):195-202. [2]Yang YH, Huang YH, Lin YL, Wang LC, Chuang YH, Yu HH, et al. Circulating IgA from acute stage of childhood Henoch-Schonlein purpura can enhance endothelial interleukin (IL)-8 production through MEK/ERK signalling pathway. Clin Exp Immunol. 2006, 144(2):247-53. [3]Weiss PF. Temporal association of Streptococcus, Staphylococcus, and parainflfluanza pediatric hospitalization and hospitalized case of Henoch-Schonlein purpura. 2010, 37(12):2587-94. [4]Rigante D. Is there a crossroad between infections, genetics, and Henoch-Schonlein purpura? Autoimmun Rev. 2013, 12(10):1016-21. [5]Pillebout E, Sunderkotter C. IgA vasculitis. Semin Immunopathol. 2021, 43(5):729-38. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.